The role of extracellular vesicles in the pathogenesis of autoimmune diseases
The investigation of extracellular vesicle (EV) biology is an innovative and rapidly growing research field. EVs are released from cells after activation or apoptosis induction. To date, two main forms of EVs can be discriminated:
Microvesicles represent large EVs (200-1000nm) released from the outer cellular membrane. As we have shown previously, these vesicles are mostly released after apoptosis induction. Exosomes are released from an intracellular compartment, the multivesicular body. These vesicles are smaller in size (50-100nm) and are mainly released after cellular activation. During the last years, we intensively studied EV biology. We and others demonstrated that EVs are important players in the regulation of immune responses. Further, a cell-to-cell transfer of genetic information by EVs has been demonstrated.
In systemic lupus erythemtosus (SLE) a dysregulated accumulation of apoptotic cells and EVs seems to be a central pathogenic feature. We have systematically characterized the release mechanisms, the morphology and molecular composition (e.g. proteins, DNA, RNA, glycokalyx) of EVs. Importantly, we demonstrated an accumulation of SLE-specific autoantigens within EVs.
The cargo of distinct EVs (exosomes/microvesicles) is tightly regulated and we have observed a directed transport of proteins and nuclear autoantigens into EVs. EVs have also been shown to influence the immunological function of a variety of responder cells: we have shown that EVs can initiate a type-1 interferon response (the marker cytokine of SLE) and an alternative maturation of dendritic cells. Upon stimulation with EVs dendritic cells from SLE patients showed a rather inflammatory phenotype when compared to normal healthy donor cells. This phenotype strictly correlated to the disease activity of the respective patient.
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